Original Article Fibroblast Growth Factor-21 Improves Pancreatic -Cell Function and Survival by Activation of Extracellular

Fibroblast growth factor-21 (FGF-21) is a recently discov-ered metabolic regulator. Here, we investigated the effects of FGF-21 in the pancreatic -cell. In rat islets and INS-1E cells, FGF-21 activated extracellular signal–regulated ki-nase 1/2 and Akt signaling pathways. In islets isolated from healthy rats, FGF-21 increased insulin mRNA and protein levels but did not potentiate glucose-induced insulin secre-tion. Islets and INS-1E cells treated with FGF-21 were partially protected from glucolipotoxicity and cytokine-induced apoptosis. In islets isolated from diabetic rodents, FGF-21 treatment increased islet insulin content and glu-cose-induced insulin secretion. Short-term treatment of normal or db/db mice with FGF-21 lowered plasma levels of insulin and improved glucose clearance compared with vehicle after oral glucose tolerance testing. Constant infu